Through the Looking-Glass, and What the Brain Sees There

She complained of recurrent attacks during which she feels that her body is growing larger and larger until it seems to occupy the whole room. “I feel,” she said, “that I have got so big that if I put out my hand I could touch the far wall.’ Less frequently, she feels that she is getting smaller, “shrinking up completely”, and that her hands will “drop off and disappear” [1].

The resemblance is so striking, this description reads like a fictitious case report of a famous literary character during her underground adventure. Instead the excerpt hails from a scientific paper published 90 years after Lewis Carroll’s novel in which Dr. John Todd describes the symptoms of 6 patients to characterize what he named Alice in Wonderland Syndrome (AIWS) as a nod to the unmistakable image it evokes [1].

Periodically she felt that her stature had altered-“the ground comes up and I go down or vice versa, so that sometimes I feel myself to be six inches tall and sometimes twelve feet” [1].

Unless you’ve just popped down a rabbit hole, feeling yourself grow and shrink is curious at best, and possibly disorienting or downright terrifying. Patients with AIWS experience distortions of visual perception, the representation of their own bodies, and even the experience of time. The most frequently described symptoms include seeing things smaller (micropsia) or larger (macropsia) than they are (58.6% and 45.0% of patients, respectively), followed by objects appearing to be farther away than they are (teleopsia, 23%), and lines and contours appearing to be wavy (dysmorphopsia, 20%) [2].

Curiouser and curiouser!

When your world looks like the distorted reflection of a funhouse mirror, a trip to a neurologist or ophthalmologist (or surely some sort of –ologist) probably seems warranted, but doctors are often unable to provide an answer as to why an AIWS patient’s vision is askew. Although attributed to infection 21-33% of the time [2,3], most often with the Epstein-Barr virus (best known as the cause of mono) [2], there is no clear cause in about half of children with these symptoms [3]. And while children make up roughly 80% of reported AIWS cases [2], the leading cause of AIWS in adults is neurologic disorders (16.8%) [2] like migraine. Early descriptions [1,4] of the syndrome go so far as to suggest Lewis Carroll, who was known to suffer from migraine headaches, was inspired by his own experiences. Some point to Carroll’s sketch of a man in which “parts of the head, shoulder, wrist, and hand are missing on the right side of the picture”—just as though one might depict a blind spot—as evidence of his visual auras (perceptual disturbances prior to migraine onset)[5]. The migraine link “arouses the suspicion that Alice trod the paths and byways of a Wonderland well known to her creator” [1], but is considered inconclusive. Less commonly, drug use, certain medications, and epilepsy have been associated with AIWS, along with an ever-growing list of conditions as more cases are reported [2].

Scientists attribute these symptoms to specific neuronal populations in the brain that respond to different types of visual information. For example the inability to perceive color (achromatopsia) or motion (akinetopsia) is attributed to the region that, when damaged, results in an inability to see color (V4) or motion (V5) [2]. Similarly, it’s thought that functional or structural abnormalities in somatosensory cortex could lead to body image distortions like microsomatognosia (experiencing the body as smaller than it is) [2]. Evidence from one subject who had an fMRI scan while experiencing micropsia indicated that symptoms arose from reduced activation in visual regions and increased activation in parietal lobe regions compared to a control [6]. While fMRI evidence from a single subject isn’t much to go on, support comes from research showing that damage to the occipital lobe can result in micropsia, and so it is thought that reduced occipital activation essentially creates a functional lesion [6] in that region. There is also evidence that seizures originating in the occipital-temporo-parietal junction can lead to both simple (e.g., micropsia) and complex (e.g. teleopsia) visual distortions [7]. If you’re keeping track you’ll notice that, as it stands now, we have a limited understanding of both the cause of AIWS and the exact functional changes in the brain that lead to it’s symptoms.

“If we were to call this “micropsia teleopsia phenomenon,” no one would care.”

-pediatric neuro-ophthalmologist Grant Liu on the importance of a catchy name

A recent review found only 169 published case descriptions of AIWS since 1955 [2]. Surprisingly, the more AIWS is studied, it seems the symptoms are hardly rare. In cross-sectional studies of children in the general population, up to 30% experience at least some individual symptoms of AIWS, though perhaps only briefly [2]. This discrepancy may be due to the fact that it is difficult to report symptoms that make you question your sanity, or that children might not find them to be particularly distressing. Concerned parents—driven by their worst fears and the alarming results that come from looking up symptoms on the internet) —often just need to be reassured that the symptoms themselves are not actually harmful. Roughly 60% of AIWS patients experience partial or total remission [2,3] and most of the time no treatment is needed [2]. Of course, there are cases when an underlying cause (e.g., epilepsy, 3% of cases) is established. Under these circumstances, unfortunately, symptoms tend to return with active phases of the disease [2] and treatment should be given for that specific condition (e.g., prescribing antiepileptics).

One pill makes you larger and one pill makes you small?

No discussion of Alice in Wonderland and visual distortions would be complete without mentioning drugs. A minority (5.4%) of AIWS cases in adults have been attributed to Hallucinogen Persisting Perception Disorder [2], in which symptoms persist following drug use. Of course, one of the other leading theories about Carroll’s inspiration for wonderland was experience with hallucinogenic mushrooms. Technically, AIWS symptoms are distortions of perception and not hallucinations, defined as perceptions in the absence of stimulus, but—as explained in a previous article on psychedelic science, “hallucinogenic” drugs rarely produce true hallucinations, but more commonly pseudo-hallucinations or perceptual distortions.

What’s difficult to grasp is just how real these visual distortions can seem. We know that perception is not reality; we don’t have sensors that detect UV light, but that doesn’t negate its existence. But our perception is the best our brain can do in response to the sensory input we receive. We tend to ignore all of the ways in which this representation is flawed and often find ourselves in disbelief when confronted with optical illusions. When the lines between what you see and what you know to be real start to blur, you may find yourself with a Cheshire cat grin thinking “we’re all mad here.”